Oxytocin regulates neurosteroid modulation of GABAA receptors in supraoptic nucleus around parturition

Jan-Jurjen Koksma, Ronald E. van Kesteren, Thomas W. Rosahl, Ruud Zwart, August B. Smit, Hartmut Lüddens, Arjen B. Brussaard

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    In this study, we investigate how neurosteroid sensitivity of GABAA receptors (GABAARs) is regulated. We examined this issue in neurons of the supraoptic nucleus (SON) of the rat and found that, during parturition, the GABAARs become insensitive to the neurosteroid allopregnanolone attributable to a shift in the balance between the activities of endogenous Ser/Thr phosphatase and PKC. In particular, a constitutive endogenous tone of oxytocin within the SON after parturition suppressed neurosteroid sensitivity of GABAARs via activation of PKC. Vice versa before parturition, during late pregnancy, application of exogenous oxytocin brings the GABAARs from a neurosteroid-sensitive mode toward a condition in which the receptors are not sensitive. This indicates that there may be an inverse causal relationship between the extent to which the GABAAR or one of its interacting proteins is phosphorylated and the neurosteroid sensitivity of the GABAAR. Neurosteroid sensitivity was not affected by changes in subunit composition of GABAARs known to occur concurrently in these cells.
    Original languageEnglish
    Pages (from-to)788-797
    Number of pages10
    JournalJournal of neuroscience
    Issue number3
    Publication statusPublished - 1 Feb 2003

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